The C-terminal domain of T4 fibritin (foldon) is obligatory for the formation of the fibritin trimer structure and has been used as an artificial trimerization domain. Its native structure consists of a trimeric β-hairpin propeller. Foldon trimerization is one of the fastest bimolecular protein associations reported in the literature.
At low pH, the foldon trimer disintegrates into a monomeric (A-state) form that has similar properties as that of an early intermediate of the trimer folding pathway. The formation of this A-state monomer from the trimer, its structure, thermodynamic stability, equilibrium association and folding dynamics have been characterized to atomic detail by modern high-resolution NMR techniques. The foldon A-state monomer forms a β-hairpin with intact and stable H-bonds that is similar to the monomer in the foldon trimer, but lacks a defined structure in its N and C-terminal parts. Suggested mechanisms for the action of the foldon imply that, as an autonomous folding domain, it is the first to trimerize, providing a “template” that brings the sequences into close proximity and correct register. By acting as a kinetic seed, the foldon can drive the correct pairing of fused domains and tether the terminal ends of the nascent structure together
The ability to trimerize proteins is of great interest for biomaterials and nanotechnology applications. The foldon domain is a versatile trimerization motif and can be combined with a variety of proteins. Further optimization of the domain for specific purposes is defined herein.